The Role of SUR1-TRPM4 Upregulation in Epilepsy Pathogenesis
Abstract number :
1.006
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2021
Submission ID :
1826628
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:55 AM
Authors :
Mitchell Moyer, BS - University of Maryland; Riccardo Serra, MD - Resident, Neurosurgery, University of Maryland; Muznabanu Bachani - Neurosurgery - University of Maryland; Svetlana Ivanova - Neurosurgery - University of Maryland; Vladimir Gerzanich, MD/PhD - Associate Professor, Neurosurgery, University of Maryland; Alexander Ksendzovsky, MD/PhD - Assistant Professor, Neurosurgery, University of Maryland; Marc Simard, MD/PhD - Professor of Neurosurgery, Neurosurgery, University of Maryland
Rationale: Current treatment for chronic epilepsy is insufficient, as antiepileptic drugs are associated with significant off-target side effects. Sur1-TRPM4 is a depolarizing sodium transporter that is not basally expressed in the healthy human brain. Recent evidence has shown hypoxia-mediated SUR1-TRPM4 expression in traumatic brain injury and stroke. Furthermore, we recently described hypoxia-associated neuronal metabolic changes in chronic epilepsy. As such, we hypothesize that chronic seizures lead to neuronal Sur1-TRPM4 upregulation which then leads to further seizures by increasing resting depolarizing sodium current.
Methods: We used a pentylenetetrazol (PTZ) kindling mouse model to evaluate for SUR1-TRPM4 expression. Mice were injected intraperitoneally with subconvulsive doses (35 mg/kg) of PTZ every other day for twenty days and monitored behaviorally and with intracranial video electroencephalogram (EEG). Immunohistochemistry was used to assess Sur1-TRPM4 expression in cerebral cortex and hippocampus of PTZ and control mice. Sur1-TRPM4 quantification was performed by manually counting cells within a 20x field demonstrating a specific signal defined by an intensity greater than a threshold of 1.5x peak fluorescent intensity. Differences between groups were compared using Student's t-test with significance defined as p< 0.05.
Basic Mechanisms